Eplerenone is a synthetic steroid with pharmacological activity as an aldosterone antagonist, whose excess in the human body is related to chronic pathological conditions including hypertension. This is not the first synthetic molecule with anti-aldosterone activity used in drug preparation but, unlike its predecessors, among which the most important is certainly spironolactone, it has a reduced hormonal activity. This characteristic leads to a decrease in undesired side effects on the endocrine system.
Eplerenone is disclosed in U.S. Pat. No. 4,559,332 of 1985.
The transformation object of the present application, the elimination of a molecule of water from intermediate (IV) to intermediate (V) depicted below
is described in WO 03/082895, in WO 98/25948 through the formation of reactive intermediates of hydroxyl in position 11 to be eliminated later on, and in WO 97/21720.
As can be easily checked in the experimental descriptions given in said patent applications, however, such reactions appear complex, burdened by the formation of considerable amounts of by-products.
Some of the examples of these documents provide no indication regarding yield and quality.
The reaction from intermediate (IV) to intermediate (V) is instead critical to the yield and the quality of the final eplerenone obtainable by oxidation of intermediate (V).
Therefore, the need to carry out the transformation from intermediate (IV) to intermediate (V) with a simple reaction, characterized by high yields and easily implemented on an industrial scale is felt.